This is a Scientist Development Award for Clinicians to develop expertise in treatment research with adolescent drug abusers. The theme of this application is prevention of career addiction through early intervention. The target group is teenagers using "gateway" (marijuana, hallucinogens and alcohol) or hard drugs (herein and cocaine). The method is detection, delineation and treatment of comorbid psychiatric disorders that increase the risk for career addition. The specific focus is on mood disorders. Since pilot data already suggest depression is detectable and treatable in this at-risk population, a double blind placebo-controlled study with fluoxetine is planned for substance abusing teenagers with unipolar spectrum disorders (major depression, dysthymia). Mood stabilizing agents are commonly prescribed in the substance abusing population, but systematic study is lacking. An open trial of a mood stabilizing agent (Depakote) is therefore proposed for substance abusing teenagers with severe mood swings meeting specified screening criteria. Although there is insufficient time in this grant to perform two clinical trials and a full family study, carefully collected family history data and treatment response will be used to develop an algorithm to predict which patients will benefit from psychopharmacologic intervention. Future career possibilities include clinical trials testing the derived predictors, with long-term follow-up and collaboration in family studies.